NGI-1 is a small molecule inhibitor of the oligosaccharyltransferase (“OST”), a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. NGI-1 has been shown to induce cell-cycle arrest accompanied by induction of p21, auto-fluorescence, and cell morphology changes, all hallmarks of senescence (Lopez-Sambrooks, et al., Nat Chem Biol. 12(12):1023-1030 (2016)). Thus, OST inhibition is a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells.
However, the use of NGI-1 in vivo has been significantly hampered by its physico-chemical properties. NGI-1 cannot be delivered in vivo by standard methods.
Therefore, it is an object of the invention to provide effective ways of delivering therapeutic, diagnostic, and/or prophylactic agents in vivo, particularly agents targeting oligosaccharyltransferases.
It is also an object of the invention to provide polymeric formulation which are suitable for in vivo delivery of therapeutic, diagnostic, and/or prophylactic agents including chemotherapeutic agents, and methods of making thereof.
It is a further object of the invention to provide methods of using polymeric formulation for systemic delivery of therapeutic agents including NGI-1 in vivo.